Renal effects of the calcium channel blocker aranidipine and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats.
The purpose of this study was to investigate the renal effects of aranidipine, a novel calcium channel blocker of the dihydropyridine type, and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats (SHRs). When infused into the renal artery in anesthetized dogs, aranidipine (0.03 microg/kg/min) induced sustained increases in urine volume and urinary excretion of sodium and of potassium. This effect was greater than that elicited by nifedipine (0.1 microg/kg/min). The aranidipine metabolite, M-1 (0.1 microg/kg/min), also caused diuresis and natriuresis almost equal to those of nifedipine. The stop-flow experiment using the anesthetized dog showed that intrarenal infusion of aranidipine (0.03 microg/kg/min), as well as nifedipine (0.1 microg/kg/min), produced natriuresis at the distal tubular site rather than at the proximal site. Aranidipine (0.3, 1, and 3 mg/kg), when administered orally, dose-dependently increased urine volume and urinary excretion of electrolytes in conscious saline-loaded SHRs. M-1 (10 mg/kg, p.o.) also showed diuretic and natriuretic effects comparable to those of nifedipine (10 mg/kg) in SHRs. In addition, after repeated oral administration of aranidipine for 7 days, short-term tolerance was not found for its diuretic and natriuretic effects in SHRs. These results suggest that, apart from antihypertensive efficiency, aranidipine may offer a therapeutic advantage by producing diuresis and natriuresis in hypertensive patients. The metabolite of aranidipine may contribute, in part, to the diuretic, natriuretic, and antihypertensive effects of aranidipine.
Ichihara
K
K
New Drug Research Laboratory, Maruko Pharmaceutical Co., Ltd., Kasugai, Japan.
Okumura
K
K
Kamei
H
H
Nagasaka
M
M
Kanda
A
A
Kanno
T
T
Miyoshi
K
K
Miyake
H
H
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000378:metabolism; D003404:Creatinine / Q000097:blood / Q000652:urine; D004095:Dihydropyridines / Q000008:administration & dosage* / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011188:Potassium / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013997:Time Factors; D014237:Trichlormethiazide / Q000494:pharmacology; D014556:Urine; D010130:p-Aminohippuric Acid / Q000097:blood / Q000652:urine
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004232:Diuretics; C059427:aranidipine; D012964:Sodium; D003404:Creatinine; D009543:Nifedipine; D014237:Trichlormethiazide; D011188:Potassium; D010130:p-Aminohippuric Acid